Scientists Found Sperm’s Power Switch (And A Way To Turn It Off)
Original article by: Megan Molteni
CONDOMS HAVE COME a long way from the linen and animal bladder sheaths used by the ancient Greeks, Romans, and Egyptians. But the tenets of modern male birth control are no different now than they were then: Keep sperm away from eggs. In the US, some 5.7 million women still rely on the male condom as their primary form of birth control.
But setting up a barrier isn’t the only way to keep sperm from fertilizing eggs. To succeed in their mission, sperm have to be good at two things: swimming and drilling. Most birth control, including condoms, targets the swimming portion of the baby-making biathlon; scientists haven’t been able to pull the plug on the sperm drilling operation itself. But now, using measurements of ion currents inside a single sperm, they’ve found the power switch&mdashand a way to turn it off. The result, they say, could be a more effective contraceptive, and one that would work equally as well in men as in women.
To make their way from the cervix, through the uterus, and into a fallopian tube, sperm cells beat their tails side to side like a snake cutting across the countryside. It’s good for covering long (relative) distances: Human sperm have to swim 10 to 12 centimeters, or 24,000 times their own body length, to reach the egg. But that tail waggle is totally useless for pushing through an egg’s thick protective layer, called the zona pellucida. That barrier stands between a sperm and its Darwinian destiny.
The head of a human sperm is just five puny microns long. To get through the 30-micron-deep zona pellucida, it has to turn its tail into a powerful drill. Instead of beating side to side, it starts to turn in only one direction, corkscrewing the head forward, through the dense, viscous environment of the egg’s outer layers. Scientists call this maneuver the “power kick.”
And what powers the power kick? A massive dump of calcium ions into the sperm’s tail. (Ion transfer across membranes is how cells generate the electricity they need to power motor function.)
While there are thousands of different kinds of ion channels in every cell in the human body, the power kick relies on just one, found only in sperm. Its name is Catsper. And it only activates to let calcium in when it gets close to an egg and encounters progesterone. Scientists have known about Catsper (the friendly, sperm-specific ion channel) since 2001, when they stumbled across it while studying male infertility. The patients, it turned out, had a mutation in at least one of the nine genes that code for Catsper.
In a paper published today in PNAS, researchers at UC Berkeley screened more than 50 chemical compounds to find a few that could tightly bind with Catsper, gumming up its channel and preventing the calcium dump needed for a power kick. The two most promising ones both come from plants that humans have been consuming for millennia: lupeol, a compound found in mangos, grapes, and olives, and pristimerin, which comes from an ancient medicinal herb known as the “Thunder God Vine.” (Presumably the thunder god didn’t also preside over matters of fertility.)
“This could be used immediately to make a better and more efficient emergency contraceptive,” says study leader and biophysicist Polina Lishko. She points out that one of the biggest controversies over current Plan B options is that they sometimes work by preventing a fertilized egg from attaching to the uterus. That debate leaves current emergency contraception options vulnerable to anti-abortion advocates who believe life starts at conception. “This method is not only 10 times more effective than anything currently on the market, but it clearly prevents fertilization,” Lishko says. “There’s no embryo at any point.”
But it’s the potential for an effective male contraceptive that has Erwin Goldberg excited. A molecular biologist and sperm researcher at Northwestern University, he says the study, from a scientific perspective, should make a compelling pitch to drug developers. “We haven’t had anything new in the realm of male contraceptives since the introduction of the condom,” he says. A number of high-profile injectable hormonal male contraceptives have failed over the years or been stopped short for concern over side effects.
One notable exception is Vasalgel, a gel-like barrier that is injected into the vas deferens to block sperm. In February it passed a primate trial, and is headed towards humans next. The Berkeley researchers are a few steps behind that, but Goldberg still thinks they’re on to something. “As far as developing a new male contraception I personally think this is an important idea,” he says. But, he points out, pharmaceutical companies still have to believe there’s a demand for that sort of thing in order to back expensive clinical trials.
The results Lishko and her team published today came from measurements they made on human sperm in the lab. But they recently began trials in primates to see how long the drill-disabling effect lasts in the body, and to work out proper doses. She expects those results later this year. They’ll be important for the plans she has to start a company and commercialize the compounds within the next three years. The goal is what Lishko calls a universal contraceptive: one that works for both men and women and could be taken either orally or released slowly through an implantable ring. That would bring some much-needed gender equity to the pregnancy prevention pantheon. No drill, no baby, no drill.